The objective of this study is to plan for a clinical trial to determine better ways to diagnose and treat acanthamoeba keratitis. Acanthamoeba keratitis is a blinding corneal infection that is an increasingly common cause of visual impairment in the United States. Acanthamoeba keratitis can be difficult to diagnose, since clinical signs are nonspecific, and cultures can be negative even if infection is present. The ideal treatment regimen is not clear. Most corneal specialists treat with multiple topical and oral agents. However, multiple agents may not be more effective than a single agent, and the use of multiple agents has the disadvantages of corneal toxicity and worse adherence. The use of topical corticosteroids for acanthamoeba keratitis is controversial. Some cornea specialists oppose the use of corticosteroids, since they have been shown to promote acanthamoeba proliferation. Others have used corticosteroids as an adjunctive therapy to reduce inflammation and pain. In this study, we expect to improve the evidence base for the diagnosis and management of acanthamoeba keratitis, through the following specific aims: 1) To determine the sensitivity and specificity of several diagnostic tests for acanthamoeba keratitis, including clinical examination, culture, smear, PCR, and confocal microscopy. 2) To determine whether patients randomized to single agent therapy for acanthamoeba keratitis with topical chlorhexidine have similar microbial cure times compared to those randomized to multiple agent therapy with topical chlorhexidine and propamidine plus oral voriconazole 3) To determine whether patients being treated for acanthamoeba keratitis who are randomized to topical corticosteroids will have better vision compared to those randomized to a placebo. Large clinical studies for acanthamoeba have traditionally proven difficult, because while the risk of acanthamoeba keratitis is significan for contact lens wearers, relatively few cases present at any one center. We address this by establishing a collaboration between 3 centers: the University of California, San Francisco, the University of Illinois at Chicago, and the Aravind Eye Hospitals in India. As a result, the proposed study would make up the largest prospective randomized study on acanthamoeba keratitis ever performed, and only the second randomized clinical trial. During the course of the planning period, we propose to finalize the study protocol and statistical analysis plan, and to start recruiting study subjects in order to assess enrollment potential. PUBLIC HEALTH RELEVANCE: This research will provide evidence on best practices for the diagnosis and treatment of acanthamoeba keratitis. The trial will lead to an understanding of (1) the utility of diagnostic tests for acanthamoeba keratitis, (2) the effectiveness of monotherapy versus combination therapy for the treatment of acanthamoeba keratitis, and (3) the potential benefit of adding topical corticosteroids. We expect this trial to enhance patient outcomes by aiding physicians in the diagnosis and treatment of acanthamoeba keratitis.